The barrier that protects the brain makes it harder to treat this essential organ

May 04, 2018 | by
CTCA

To protect the brain, the body has developed a series of defenses to keep it safe from harm—from both internal and external threats.

The brain is the body's traffic cop, computer processor, electric power supply and emotional arbiter, all in one amazing organ. To borrow from a famous song, every breath we take, every move we make is a function of the brain. To protect this vital organ, the body has developed a series of defenses to keep the brain safe from harm—from both internal and external threats. On the outside, the brain is protected by a 6- to 7-millimeter layer of bone commonly known as the skull, while several layers of liquid called meninges cushion the brain from the inside. The brain also is protected by a physical and biochemical wall called the blood-brain barrier that blocks toxins from reaching brain cells. These defenses, in particular the blood-brain barrier, also make it more difficult to treat disease of the brain, including cancer. But scientists are working to find ways to penetrate, bypass or open the barrier to allow more effective treatments for brain diseases.

“The blood-brain barrier has been recognized to be a major issue when using systemic therapy for known or suspected cancer in the brain or spinal cord.” - Maurie Markman, MD, President of Medicine & Science at Cancer Treatment Centers of America® (CTCA)

The blood-brain barrier is made up mostly of endothelial cells, which line glands, organs and blood vessels throughout the body. In most cases, endothelial cells have gaps in their membranes that allow essential substances, like medicines, to flow in and out of the bloodstream. In the brain, however, those gaps are sealed with proteins that limit what can pass through. The barrier also contains astrocytes, star-shaped cells that act as the barrier's gatekeepers, determining what gets in and what's kept out. Allowed: essentials such as oxygen and glucose that allow the brain to function. Barred at the barrier: toxins and bacteria that can harm the brain or cause infection.

But the barrier also keeps out many substances that are meant to help the brain, including drugs designed to treat brain cancer. For instance, chemotherapy drugs, designed to kill fast-growing cells like cancer cells, may also kill fast-growing cells elsewhere in the body. The cells of the blood-brain barrier may consider these drugs too toxic to be allowed access to the brain, preventing them from reaching the cancer. Cells in the barrier also have large amounts of a protein called P-glycoprotein (P-gp), which helps flush toxins out of cells. So even if a chemotherapy drug were to penetrate a brain cell, P-gp may promptly remove it. "No matter what drugs you use systemically, there is a blood-brain barrier," says Shayma Master Kazmi, MD, RPh, Hematologist-Oncologist and Medical Oncologist at our hospital in Philadelphia. "So a lot of chemotherapy drugs or immunotherapy drugs don’t get close to 100 percent penetration into the central nervous system. If the drug isn’t getting to where it needs to go, that's problem No 1."

PENETRATING THE BARRIER

Researchers and scientists have searched for more direct ways to penetrate the barrier and reach the brain, including:

Direct injection: Doctors have injected viruses directly into brain tumors to help stimulate an immune response. The treatment, called oncolytic virus therapy, was featured in a CBS 60 Minutes report detailing a Duke University clinical trial on a treatment for glioblastoma, the most aggressive form of brain cancer. The U.S. Food and Drug Administration (FDA) in 2017 called the treatment a "breakthrough therapy," allowing for an accelerated process to develop new treatments based on the therapy. Still, the FDA has not approved the treatment, and concerns have been raised about the therapy’s potential drawbacks and limitations. It can’t reach some tumors, for example, and it often causes some serious side effects. "It is uncertain how well these therapies are distributed throughout the tumor in the absence of delivery by blood flow," Dr. Markman says. "And the ability to directly penetrate into some tumor masses is highly questionable."

Radio waves: Researchers in Switzerland claim to have extended the life of some glioblastoma patients, by using electromagnetic-wave treatment in combination with chemotherapy. Electromagnetic waves are believed to disrupt cancer cells and prevent them from growing. Patients were required to wear a cap dotted with electrodes for at least 18 hours a day. "It’s not the easiest thing in the world to do," Dr. Kazmi said. "That's a tough sell."

Clinical trials are underway in search of ways to penetrate the blood-brain barrier to treat not just cancer, but other diseases of the brain, such as Alzheimer's and multiple sclerosis, as well as traumatic brain injuries. What researchers continue to find is that the barrier, like the brain, is complex and not easily penetrated. "It's a protective barrier created by the brain, because the human body is brilliant," Dr. Kazmi says. "The most important part of the body is the brain. The brain will always protect itself so most harmful chemicals don't penetrate it."